Composition of traditional chinese medicines for preventing and treating cerebrovascular disease

ABSTRACT

The present invention provides a composition including at least six of the following traditional Chinese medicines: Ren Shen, Dang Gui, Huang Qi, Gan Cao, Chai Hu, Huang Lian, Tian Zhu Huang, Huang Qin. The composition possesses pharmaceutical activities of inhibiting platelet aggregation and prolonging bleeding time, and can be used in preventing and treating a cerebrovascular disease.

FIELD OF THE INVENTION

The present invention relates to a composition of traditional Chinesemedicines possessing activities of inhibiting platelet aggregation andprolonging bleeding time, which can be used to prevent and treatischemic cerebrovascular disease (ischemic stroke).

BACKGROUND OF THE INVENTION

So far, certain Chinese medicines may claim to have pharmacologicalactivity in inhibiting platelet aggregation or prolong bleeding time,yet no Chinese medicines are proved to possess significantpharmacological potential in preventing and treating ischemiccerebrovascular disease.

SUMMARY OF THE INVENTION

The present invention provides a novel composition of traditionalChinese medicines.

More specifically, the present invention is related to a novelcomposition of traditional Chinese medicines with an activity ofinhibiting platelet aggregation.

Also, the present invention is related to a novel composition oftraditional Chinese medicines that can prolong bleeding time.

Further, the present invention is related to a novel composition oftraditional Chinese medicines that can be used in preventing andtreating cerebrovascular disease, and in particular ischemiccerebrovascular disease.

Meanwhile, the present invention also discloses a use of traditionalChinese medicines in the manufacture of a medicament for preventing andtreating cerebrovascular disease in a patient, and in particularischemic cerebrovascular disease.

The novel composition of traditional Chinese medicines of the presentinvention comprises at least six of the followings: Ren Shen, Dang Gui,Huang Qi, Gan Cao, Chai Hu, Huang Lian, Tian Zhu Huang, Huang Qin. Thesetraditional Chinese medicines are translated into English according totheir pronunciations in Mandarin.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows Chinese characters of the traditional Chinese medicinesused in the present invention, and their English translations accordingto their pronunciations in Mandarin.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a novel composition of traditionalChinese medicines comprising at least six, preferably seven, and morepreferably all, of the followings: Ren Shen, Dang Gui, Huang Qi, GanCao, Chai Hu, Huang Lian, Tian Zhu Huang, Huang Qin. These traditionalChinese medicines are translated into English according to theirpronunciations in Mandarin, and their Chinese characters are shown inFIG. 1. When the composition of traditional Chinese medicines of thepresent invention comprises six traditional Chinese medicines, Chai Huand Huang Lian are omitted. When the composition of traditional Chinesemedicines of the present invention comprises seven traditional Chinesemedicines, Huang Lian is omitted.

The present invention also discloses a use of the composition oftraditional Chinese medicines of the present invention in themanufacture of a medicament for preventing and treating acerebrovascular disease, preferably an ischemic cerebrovascular disease,in a patient.

The present invention further discloses a method of preventing andtreating a cerebrovascular disease, preferably an ischemiccerebrovascular disease, in a patient, which comprises administering tothe patient a therapeutically-effective amount of the composition oftraditional Chinese medicines of the present invention.

The composition of traditional Chinese medicines, prepared according toone of the preferred embodiments of the present invention, wasdemonstrated to possess pharmaceutical activities of inhibiting plateletaggregation and prolonging bleeding time. The same composition oftraditional Chinese medicines was also proven to possess therapeuticeffect on preventing and treating an ischemic cerebrovascular diseasethrough animal experiments, and shown having no safety concern throughsafety pharmaceutical tests and subacute toxicology tests (28 days).

Preferably, the eight traditional Chinese medicines are in the form ofdry powder. The eight traditional Chinese medicines can be obtained fromthe general traditional Chinese medicine store, which are processedseparately, baked to dry and grinded into powder.

According to the present invention, the ratio (by weight) of the eighttraditional Chinese medicines is, preferably, Ren Shen: Dang Gui: HuangQi: Gan Cao: Chai Hu: Huang Lian: Tian Zhu Huang: Huang Qin=140±10%:166±10%: 180±10%: 67±10%: 140±10%: 120±10%: 120±10%: 67±10%. The amountof the one or two unused traditional Chinese medicines are zero, whilethe weight ratio of the others remaining unchanged, in the case when thecomposition of the present invention comprises six or seven traditionalChinese medicines out of the eight traditional Chinese medicines.

The composition of traditional Chinese medicines of the presentinvention is suitable to be administered orally.

Ren Shen (Ginseng radix) used in the present invention includes (but notlimited to) Panax ginseng C.A. Meyer and Panax quinquefolium Linnaeus,and the former is preferred. Ren Shen acquired from the traditionalChinese medicine stores or trading companies is processed by steamingRen Shen in a meshed steamer with a mixture of pure water and rice wine(3:1), which is quickly boiled with a strong fire and then with a mildflame for 90 minutes; drying and slicing the steamed Ren Shen aftercooling down. Then, the Ren Shen ginseng slices are placed in an oven,and baked at 50° C. for 13 hours, and grinded into powder. One thousandgrams of Ren Shen (Panax ginseng C.A. Meyer) become approximately 930grams after the processing.

Dang Gui (Angelica sinensis radix) used in the present inventionincludes (but not limited to) the root of Angelica sinensis (Oliv.)Diels. The unsliced Dang Gui, acquired from the traditional Chinesemedicine stores or trading companies, is processed by quickly washing itwith water spray until the waste water becomes clear, and then washingwith distilled water. The clean Dang Gui (20 kg) is steamed in a meshedsteamer by boiling a mixture of 3 kg of R.O. water, 1 kg of rice wine,and 100 gm of Cyperi Rhizoma (Cyperus rotundus L.), which is quicklyboiled with a strong fire and then with a mild flame for 60 minutes, andsliced after cooling down. The Dang Gui slices are placed in anautomated oven, baked for 10 hours at 55° C., and grinded into powder.One thousand grams of Dang Gui become approximately 600 grams afterbeing processed to dry powder. According to U.S. Pat. No. 4,843,067,both Levisticum officinale Koch and Angelica archangelica can becontemplated as a substitute of Dang Gui.

Huang Qi (Astragali radix) used in the present invention includes (butnot limited to) the roots of Astragalus membranaceus (Fisch.) Bunge var.membranaceus, Astragalus membranaceus (Fisch.) Bunge var. mongholicus(Bunge) Hsiao, and Hedysarum polybotrys Hand.-Mazz. Huang Qi, acquiredfrom traditional Chinese medicine stores or trading companies, isprocessed, which comprises washing Huang Qi with water, slicing, dryingit by baking it in an oven at 50° C. for 16 hours, and grinding thedried slices into powder. One thousand grams of Huang Qi becomeapproximately 650 grams after the processing.

Gan Cao used in the present invention is the rhizome of Glycyrrhizauralensis Fisch., Glycyrrhiza glabra L. or Glycyrrhiza inflata Bat. andpreferably Glycyrrhiza uralensis Fisch. Gan Cao, acquired fromtraditional Chinese medicine stores or suppliers, is processed bywater-washing, slicing, baking at 50° C. for 12 hours, and grinding intopowder. One thousand grams of Gan Cao become approximately 720 gramsafter the processing.

Chai Hu (Bupleurum radix) used in the present invention is the roots ofBupleurm chinensis DC, Bupleurum scorzonerifolium Willd., and otherplants in the same genus, and preferably is the root of Bupleurmchinensis DC. Chai Hu, acquired from traditional Chinese medicine storesor suppliers, is processed by water-washing, drying by baking for 12hours, and grinding into powder. One thousand grams of Chai Hu becomeapproximately 720 grams after the processing.

Huang Lian used in the present invention is rhizome of Coptis chinensisFranch., Coptis deltoidea C.Y. Cheng et Hsiao, Coptis teetoides C.Y.Cheng, and other plants in the same genus. Huang Lian, acquired fromtraditional Chinese medicine stores or suppliers, is processed bywater-washing, baking at 50° C. for 12 hours, and grinding into powder.One thousand grams of Huang Lian become approximately 750 grams afterthe processing.

Tian Zhu Huang (Bambusae concretio silicea) used in the presentinvention is a bulk accumulated between nodes of a stem ofPhylllostachys nigra MUNRO var. henonis STAPF ex RENDLE) and otherplants in the same genus. Tian Zhu Huang, acquired from traditionalChinese medicine stores or suppliers, is screened by choosing thosefloating on water, which is baked at 55° C. for 18 hours, and grindedinto powder. One thousand grams of Tian Zhu Huang become approximately850 grams after the processing.

Huang Qin (Scutellariae radix) used in the present invention is the rootof Scutellaria baicalensis Georgi. Huang Qin, acquired from traditionalChinese medicine stores or suppliers, is processed by washing it withwater. The clean Huang Qin (10 kg) is steamed in a meshed steamer byboiling a mixture of 3 kg of R.O. water and 100 gm of Corni Fructus,which is quickly boiled with a strong fire and then with a mild flamefor 60 minutes, and sliced after cooling down. The Huang Qin slices areplaced in an automated oven, baked for 11 hours at 50° C., and grindedinto powder. One thousand grams of Huang Qin become approximately 700grams after the processing.

PREPARATION EXAMPLE

Panax ginseng, Dang Gui, Huang Qi, Gan Cao, Chai Hu, Huang Lian, TianZhu Huang, Huang Qin were purchased from traditional Chinese medicinesuppliers. Based on the source identification, Panax ginseng belonged toPanax ginseng C.A. Meyer, Dang Gui belonged to Angelica sinensis (Oliv.)Diels, Huang Qi belonged to Hedysarum polybotrys Hand.-Mazz., Gan Caobelonged to Glycyrrhiza uralensis Fisch., Chai Hu belonged to Bupleurumlongesadiatum Turca., Huang Lian belonged to Coptis chinensis Franch.,Tian Zhu Huang was from Bambusa textilis McCluture; Schizostachyumchinense Rendle, and Huang Qin belonged to Scutellaria baicalensisGeorgi. These eight traditional Chinese medicines were processedaccording to the processing steps described above, the resulting drypowders were sieved with a mesh No. 10 sieve, and the penetratedportions were used.

The eight traditional Chinese medicines in the powder form were mixedaccording to the following weight ratio: Panax ginseng: Dang Gui: HuangQi: Gan Cao: Chai Hu: Huang Lian: Tian Zhu Huang: Huang Qin=140: 166:180: 67: 140: 120: 120: 67, and a powder pharmaceutical composition wasobtained, which is named as BNG-1.

Example 1

1. Test substance and Dosing pattern

BNG-1 was provided by BrainGenesis Biotechnology Co., Ltd., Taiwan, anddissolved in distilled water. For oral administration (PO) in in vivotesting, the dosage is 20 ml/kg for mice. Tested animals received aninitial dosage of 1000 mg/kg daily for 8 consecutive days. For in vitroassays, 0.1 ml of testing material was added to the 10 ml bath to give afinal concentration of 1000 μg/ml, and incubated with isolated tissuesfor 5 minutes before evaluation of possible agonist response orchallenge with agonists in the Arachidonic Acid Platelet Aggregation.

2. Animals

In these studies, male/female ICR derived mice, and New Zealand derivedalbino male/female rabbits provided by animal breeding center of MDSPanlabs Taiwan, Ltd. were used. All animals were maintained in acontrolled temperature (22° C.-24° C.) and humidity (60%-80%)environment with 12 hours light dark cycles for at least one week in MDSPanlabs Taiwan laboratory prior to be used.

3. Method

Arachidonic Acid, Platelet Aggregation Agonism/Antagonism

Venous blood obtained from male or female New Zealand derived albinorabbits weighing 2.5-3 kg was used. Blood sample was mixed withone-tenth volume of trisodium citrate (0.13M) and centrifuged at roomtemperature for 10 min at 220 g. Testing substance by volume of 0.025 mlwas added to the 0.45 ml tissue bath to get a testing concentration of1000 μg/mL. The aggregation of the platelet enriched plasma (6×10⁸platelets/ml) by 50 percent or more (≧50%) within 5 minutes, relative to100 μM Arachidonic acid control response at 37° C. as measured by anoptical aggregometer, indicated possible Arachidonic acid receptoragonist activity. At a test substance concentration where no significantagonist activity was seen, the ability to reduce the Arachidonicacid-induced maximum non-reversible aggregation response by −50 percentor more (≧50%) indicated Arachidonic acid receptor antagonist activity.Each concentration was tested two separate preparations.

The concentration of 50% inhibition of aggregation induced by 100 μMArachidonic acid (IC₅₀) of BNG-1 was also determined, which is 176.5μg/ml.

Bleeding Time (PO)

A group of 5 ICR derived male mice weighing 22±2 g was administered POat the dosage of 1000 mg/kg daily for seven days and one dosage of 1000mg/kg was administered orally one hour before standardized transectionof the tip (0.5 mm) of each tail on the eighth day. The mice, inholders, were immediately suspended vertically with the distal 2 cm ofeach tail immersed in a test tube containing saline at 37° C. The timerequired for bleeding to cease over a period of 15 seconds was thendetermined. A maximun cut-off time of 180 seconds was set. Prolongationof bleeding time by 50 percent or more (≧50%) relative to a controlgroup of animals was considered significant.

4. Results: AA-platelet Agg - in vitro 1000 μ/ml 100% n = 2 antagAA-platelet Agg - in vitro 300 μg/ml 100% n = 2 antag AA-platelet Agg -in vitro 100 μg/ml 0% n = 2 antag Bleeding time PO 1000 mg/kg × 8 60% n= 5 Bleeding time PO 1000 mg/kg × 8 63% repeat n = 5 Bleeding time PO300 mg/kg × 8 0% n = 5Control Example 1

BNG-4, BNG-5, BNG-6 and BNG-7 were prepared similarly as BNG-1 inPreparation Example, except that some of the eight Chinese herbmedicines of BNG-1 were omitted while the weight proportions remainingthe same.

The procedures of Arachidonic Acid, Platelet AggregationAgonism/Antagonism test method in Example 1 were repeated to determineIC₅₀ of BNG-4, BNG-5, BNG-6 and BNG-7. The formulas and results ofBNG-4, BNG-5, BNG-6 and BNG-7 are shown as follows in comparison withIC₅₀ of BNG-1.

IC₅₀ (concentration of 50% inhibition of aggregation induced by 100 μMTest substance Arachidonic acid) BNG-1 176.5 μg/ml BNG-4 (Dang Gui andHuang Qi 406.6 μg/ml omitted) BNG-5 (Dang Gui and Chai Hu 379.2 μg/mlomitted) BNG-6 (Huang Qin and Huang Lian 393.7 μg/ml omitted) BNG-7(Dang Gui, Chai Hu, >1000 μg/ml Huang Qin and Huang Lian omitted)

Example 2

1. Test Substances and Dosing Pattern

-   Group 1 (5 rats): Vehicle Control

Saline was given orally (PO) in a dosage of 10 mL/kg immediately afterMCAO and day 1, then every 24 hours for 7 consecutive days totally.

-   Group 2 (5 rats): Positive Control (MK-801)

MK-801 was given by intraperitoneally (IP) injection at a dose of 0.3mg/kg in a dosage of 5 mL/kg at 0, 6, 24, 30, 48 and 54 hours afterMCAO.

-   Group 3 (5 rats): BNG-1 treatment

BNG-1 dissolved in saline was given orally (PO) at a dosage of 1000mg/kg in a dosing volume of 10 mL/kg immediately after MCAO on day 1,then every 24 hours for 7 consecutive days in total.

2. Animals

Male Sprauge Dawely rats weighting 180-240 g (10 weeks of age) from theAnimal Resources Center, Medical College of National Taiwan Universitywere used. The animals were maintained in a controlled temperature (22°C.-24° C.) and humidity (60%-80%) environment with 12 hour light darkcycles (6:00 a.m./6:00 p.m.) for at least one week in MDS PanlabsTaiwan, Ltd laboratory prior to use.

3. Equipment

Dental drill (UPOWER UG 33, SELECTOR-M), Image Analyzer (Life ScienceResources VISTA Version 3.0), Infant Incubator (Brighten Life BL-90-SC),Magnifying stereomicroscope (ZEISS, Stemi 1000), Microscissors (A.Heiss), Microtome (SHANDON, Varistain 24-4 Automatic Slide, U.K.) andRectal thermistor probe (Harvard Homeothermic Blanket Control Unit) wereused.

4. METHODS

-   Brain Ischemia, Middle Cerebral Artery Occlusion (MCAO)

Permanent brain ischemia via middle cerebral artery occlusion (MCAO) wascarried out under chloral hydrate (500 mg/10 mL/kg IP) anesthetized. Thetemporoparietal region was shaved and a skin incision was made betweenthe lateral aspect of the orbit and the external acoustic meatus. Thesuperior pole of the parotid gland was reflected downwards as was thetemporalis muscle after partial resection of its cranial insertion. Thedistal course of the middle cerebral artery was then visible through thetranslucent skull.

Under a 10× magnifying stereomicroscope, craniectomy was performed witha dental drill and then enlarged with fine synovectomy rongeurs. Themiddle cerebral artery at the proximal site of branch originated frominterior carotid artery was cut with a microscissors after which thetemporalis muscle and parotid gland were replaced. The incision waslightly dusted with kanamycin, the scalp was sutured and a 10% povidoneiodine solution was topically applied. During surgery, the animals weremaintained normothermic by means of a homeothermic heating systemcoupled to a rectal thermistor probe. Under these conditions, rectaltemperature was maintained within physiological limits (37.5±1.0° C.).After surgery, animals were kept in infant incubator (37.5±1.0° C.)while recovering from anesthesia for 1 hour. After recovery, the ratswere housed 5 per cage with free access to food and water and kept in aclean animal room (23.0±10° C.).

BNG-1, dissolved in saline as vehicle, was administered at doses of 1000mg/kg (n=5) orally (PO) in a dosing volume of 10 ml/kg daily for 7consecutively days started immediately after MCAO. The vehicle-controlgroup (n=5) was similarly treated with saline alone. The positivecontrol reference agent MK-801 (RBI, Natick, Mass. 01760-2447, U.S.)dissolved with saline was injected at a dose of 0.3 mg/kgintraperitoneally (IP) in a dosing volume of 5 ml/kg at 0, 6, 24, 30, 48and 54 hours after MCAO.

On the eighth day after the ischemic insult, all animals were sacrificedby decapitation. Their brains were rapidly removed and immediatelyfrozen at −70° C. in deep freezer (NUAIR™, NU-6511). Twenty-four hourslater, whole brain coronal sections (30 μm) were obtained by use of amicrotome (“SHANDON” Varistain 24-4 Automatic Slide). Every 13^(th)section (i.e. 390 μm apart) totally covering the infarction area of 12mm length was selected for histological examination. Altogether 30slices, stained by 2% cresyl violet, were used to measure the area ofischemic damage. This was quantitatively assessed by an Image Analyzer.The total ischemic area (mm²) of each coronal slice from each animal wassummated and expressed as the mean±SEM. The calculated infarcted volume(mm³) of mm²×specific distance (390 μm) was then expressed as themean±SEM for each experiment group. The effect of BNG-1 and MK-801treatment was calculated for comparison with the vehicle control groupby means of the unpaired Student's t test, differences were consideredsignificant at *P<0.05. For each animal, body temperature was recordedbefore 0 minutes (pre-dosage) and 30 minutes (post-dosage) after eachoral administration. Tukey multiple comparison test was applied forcomparison between pre-dosage and post-dosage temperatures.

5. Results

BNG-1, evaluated at a dose of 1000 mg/kg PO for 7 consecutive dayspost-treatment, significantly reduced (46.29%) brain ischemia in ratssubjected to unilateral and permanent middle cerebral artery occlusion.No toxicity or mortality was observed in tested animals during the 7consecutive days study. No significant change in body temperature wasobserved. MK-801 significantly reduced (48.38%) brain ischemia.

Example 3

Permanent brain ischemia via middle cerebral artery occlusion (MCAO) wascarried out to Male Sprange Dawely rats by the same procedures as inExample 2.

BNG-1, dissolved saline as vehicle, was administered at doses of 1000mg/kg and 500 mg/kg orally (PO) for 7 days daily before and for 3 daysdaily after MCAO. The vehicle-control group was similarly treated withsaline alone. The positive control reference agent MK-801 was injectedintraperitoneally (IP) at a dose of 0.3 mg/5 ml/kg immediately afterMCAO 0, and again after 6, 24, 30, 48 and 54 hrs. On the fourth day theischemic insult, all animals were sacrificed by decapitaiton. The totalischemic area of their brains were determined according to the sameprocedures as in Example 2.

Under the experimental conditions used, MCAO caused a reproducibleischemia of around 50%-60% of the affected hemisphere. For the mostpart, the area of damage was largely confined to various corticalregions (i.e. frontal, sensorimotor, auditory and occipital cortices)and only rarely involved damage to components of the basal ganglia.Relative to the vehicle-treated control group, MK-801 significantlyreduced the total infarcted volume by 66.30±10.50% at a dose of 0.3mg/kg IP×6. At the 1000 mg/kg PO ×10 dose level, BNG-1 significantlyreduced the total infarcted volume of 44.09±9.01% while anon-significant 14.17±19.43% reduction was observed after the 500mg/kg×10. None of the compounds caused any significant change in bodytemperature.

The SAFETY PHARMACOLOGY of BNG-1 was evaluated according to the SAFETYPHARMACOLOGY testing package (non-GLP) undertaken at MDS Panlabs Taiwan,Ltd., Taiwan.

SAFETY PHARMACOLOGY test results Administration Dosage or Experimentsroute concentration Activity Mice behavior reaction-Irwin oral 0.5, 1.0and No effect observation screening (General 2.0 (gm/kg) behavioral,autonomic, neurological sign, etc, 38 tests and 7 days toxicity lethalrate observation) Central nervous system (spontaneous oral 0.5, 1.0 andNo effect activity motor in coordination, 2.0 (gm/kg) prolongation ofhexobarbital sleeping time, protection against maximal-electroshock orpentylenetetrazole-induced convulsions and mortality, proconvulsant oranticonvulsant response and analgesic activity (tail flick response andphenylquinone-induced writhing) in mice and body temperature in rats)Respiration-circulation system oral   1 (gm/kg) No effect (Alteration ofmean, systolic and diastolic blood pressure, femoral blood flow, heartrate, QT interval, PR interval, QRS duration and S-T segment andrespiratory rate in dogs) Urine volume output, electrolyte oral   1(gm/kg) No effect excretion and urinary pH values in ratsGastrointestinal system (Gastrointestinal oral   1 (gm/kg) No effectMotility in mice) Contractile responses of guinea pig In vitro   1(mg/ml) Reduced ileum induced by Acetylcholine, contractile Histamine,and Barium Chloride Contractile responses of guinea pig In vitro 0.3(mg/ml) Reduced ileum induced by Acetylcholine contractile

The result suggests that it should not have safety concern when orallyapplying 1 gm/kg of BNG-1 to rats.

-   The acute toxicity test of BNG-1

Singe dosage of BNG-1 viscous suspension (5gm/kg) was orally apply to 6male and 6 female rats, control groups were applied with controlsolution without test material(1% CMC solution), and the acute toxicityof BNG-1 to rats was determined. Each rat was administered with twice (2hours interval) of BNG-1 or control solution, undergo clinicalobservation for 14 days. None of them show any clinical toxicitysymptom, and no symptom was observed either in organs or tissues by bareeyes after dissecting the rats. Hence, with 5 gm/kg dosage of BNG-1, itdid not cause any observable acute toxicity in rats. Therefore, 5 gm/kgis the “no observable effect level” (NOEL) for BNG-1, and can beclassified as practically nontoxic material.

To summarize the test results obtained in the above, it suggests thatBNG-1, in 1 gm/kg, can prevent and treat ischemic cerebrovasculardisease in mice; and in that dosage, it should not has any safetyconcern, and it does not show acute toxicity. These results evidencethat BNG- 1 has a great potential of preventing and treating ischemiccerebrovascular disease in human.

It also has been found that, under in vitro administration with 1 mg/mlof BNG-1, 67% relaxation activity against the spontaneous tension ofrespiratory tract in guinea pig ileum was observed, and 31% enhancementin contraction force of myocardium of guinea pig ileum was alsoobserved.

Although the present invention has been described with reference tospecific details of certain embodiments thereof, it is not intended thatsuch details should be regarded as limitations upon the scope of theinvention except as and to the extent that they are included in theaccompanying claims. Many modifications and variations are possible inlight of the above disclosure.

1. A pharmaceutical composition for inhibiting platelet aggregationcomprising an effective amount of the following eight medicines, RenShen, Dang Gui, Huang Qi, Gan Cao, Chai Hu, Huang Lian, Tian Zhu Huang,and Huang Qin as active ingredients.
 2. The pharmaceutical compositionaccording to claim 1, wherein said eight medicines are in the form ofdry powder.
 3. The pharmaceutical composition according to claim 2,wherein said eight medicines are in a weight ratio of Ren Shen Dang GuiHuang Qi: Gan Cao Chai Hu: Huang Lian: Tian Zhu Huang Huang Qin=140±10%:166±10%: 180±10%: 67±10%: 140±10%: 120±10%: 120±10%: 67±10%.
 4. Thepharmaceutical composition according to claim 3, which is administeredorally.
 5. A pharmaceutical composition for prolonging bleeding time ina patient comprising an effective amount of the following eightmedicines, Ren Shen, Dang Gui, Huang Qi, Gan Gao, Chai Hu, Huang Lian,Tian Zhu Huang, and Huang Qin, as active ingredients.
 6. Thepharmaceutical composition according to claim 5, wherein said eightmedicines are in the form of dry powder.
 7. The pharmaceuticalcomposition according to claim 6, wherein said eight medicines are in aweight ratio of Ren Shen: Dang Gui Huang Qi: Gan Gao: Chai Hu: HuangLian: Tian Zhu Huang: Huang Qin=140±10%: 166±10%: 180±10%: 67±10%:140±10%: 120±10%: 120±10%: 67±10%.
 8. The pharmaceutical compositionaccording to claim 7, which is administered orally.
 9. A pharmaceuticalcomposition for treating an ischemic cerebrovascular disease in apatient comprising an effective amount of the following eight medicines,Ren Shen, Dang Gui, Huang Qi, Gan Cao, Chai Hu, Huang Lian, Tian ZhuHuang, and Huang Qin, as active ingredients.
 10. The pharmaceuticalcomposition according to claim 9, wherein said medicines are in the formof dry powder.
 11. The pharmaceutical composition according to claim 10,wherein said eight medicines are in a weight ratio of Ren Shen: DangGui: Huang Qi: Gan Gao: Chai Hu: Huang Lian: Tian Zhu Huang: HuangQin=140±10%: 166±10%: 180±10%: 67±10%: 140±10%: 120±10%: 120±10%:67±10%.
 12. The pharmaceutical composition according to claim 11, whichis administered orally.